Antibodies (also called immunoglobulins) are glycoproteins, which specifically recognize foreign molecules. These recognized foreign molecules are called antigens. When antigens invade humans or animals, an immunological response is triggered which involves the production of antibodies by B-lymphocytes. By this immunological response, microorganisms, larger parasites, viruses and bacterial toxins can be rendered harmless. The unique ability of antibodies to specifically recognize and bind with high affinity to virtually any type of antigen makes them useful molecules in medical and scientific research.
In vertebrates five immunoglobulin classes are described, including IgG, IgM, IgA, IgD and IgE, all of which differ in their function in the immune system. IgGs are the most abundant immunoglobulins in the blood. They have a basic structure of two identical heavy (H) chain polypeptides and two identical light (L) chain polypeptides. The H and chains are kept together by disulfide bridges and non-covalent bonds. The chains themselves can be divided in variable and constant domains. The variable domains of the heavy and light chain (VH and VL), which are extremely variable in amino acid sequences, are located at the N-terminal part of the antibody molecule. VH and VL together form the unique antigen-recognition site. The amino acid sequences of the remaining C-terminal domains are much less variable and are called CH1, CH2, CH3 and CL. The non-antigen binding part of an antibody molecule is called the constant domain Fc and mediates several immunological functions, such as binding to receptors on target cells and complement fixation.
The unique antigen-binding site of an antibody consists of the heavy and light chain variable domains (VH and VL). Each domain contains four framework regions (FR) and three regions called CDRs (complementarity determining regions) or hypervariable regions. The CDRs strongly vary in sequence and determine the specificity of the antibody. VL and VH domains together form a binding site, which binds a specific antigen.
Exemplary foreign bodies include a wide variety of viruses, such as norovirus. Norovirus, for example, is a genus of genetically diverse single-stranded RNA, non-enveloped viruses in the Caliciviridae family. The known viruses in the genus are all considered to be the variant strains of a single species called Norwalk virus. The viruses are known to be transmitted by fecally contaminated food or water, by person-to-person contact, and via aerosolization of the virus and subsequent contamination of surfaces. Noroviruses are the most common cause of viral gastroenteritis in humans and affect people of all ages.
Norovirus infection is characterized by nausea, forceful vomiting, watery diarrhea, abdominal pain, and in some cases, loss of taste. General lethargy, weakness, muscle aches, headache, and low-grade fever may occur. The disease is usually self-limiting, and severe illness is rare. Although having norovirus can be unpleasant, it is not usually dangerous and most individuals that contract it make a full recovery within a couple of days. However, the virus affects around 267 million people and causes over 200,000 deaths each year.
After infection, immunity to norovirus is usually incomplete and temporary. Outbreaks of norovirus infection often occur in closed or semiclosed environments, such as long-term care facilities, overnight camps, hospitals, schools, prisons, dormitories, and cruise ships, where the infection spreads very rapidly either by person-to-person transmission or through contaminated food. For example, many norovirus outbreaks have been traced to food that was handled by one infected person.
Moreover, viruses (e.g., norovirus) can often evolve or mutate over time. In some cases the evolution of viruses can occur rather rapidly, which makes screening, identification and distribution of neutralizing antibodies in a timely and cost-effective manner particularly difficult.
Accordingly, there remains a need for a cost-effective and timely approach to maintain efficacy of therapeutic antibodies as viruses (e.g., norovirus) evolve.